Methanol → HCID 86698851, compound

HRID 1054871Notes

Reaction equation

HRID 1054871 reaction equation
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([C@@H:17]3[CH2:21][CH2:20][CH2:19][O:18]3)=[CH:13][CH:12]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([C:23]([OH:25])=[O:24])=[CH:5][NH:6]2.CO>C(=O)=O>[F:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([CH:17]3[CH2:21][CH2:20][CH2:19][O:18]3)=[CH:15][CH:16]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([C:23]([OH:25])=[O:24])=[CH:5][NH:6]2

Participants

4

Reactant 2

HCID 887Methanol2×HCID 86698852HCID 86698852, compound

Product 1

HCID 86698851HCID 86698851, compound

Reagents, catalysts & solvents 1

HCID 280Carbon DioxideSolvent2×

Procedure

Racemic-4,6-difluoro-5-[4-(tetrahydrofuran-2-yl)phenyl]-1H-indole-3-carboxylic acid was subjected to separation by preparative SFC (Column: OJ (250 MM*30 MM, 5 UM); Mobile phase: 30% MEOH NH3H2O 60 ML/MIN 3; Wavelength: 220 nm) Peak 1 was isolated and arbitrarily called 4,6-difluoro-5-{4-[(2S)-tetrahydrofuran-2-yl]phenyl}-1H-indole-3-carboxylic acid. Peak 1 was isolated as Isomer 1 (Example 152) Retention time=8.43 min; Column: Chiralcel OJ-H 250×4.6 mm I.D., 5 um Mobile phase: methanol (0.05% DEA) in CO2 from 5% to 40% Flow rate: 2.5 mL/min Wavelength: 220 nm. MS (ES+) 343.8 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 8.06 (s, 1 H) 7.42 (m, 5 H) 7.25 (d, 1 H) 4.88 (t, 1 H) 4.03 (q, 1 H) 3.85 (q, 1 H) 2.35 (m, 1 H) 1.99 (m, 2 H) 1.75 (m, 1 H). Peak 2 was isolated as Isomer 2 (Example 153), Retention time=8.86 min; Column: Chiralcel OJ-H 250×4.6 mm I.D., 5 um Mobile phase: methanol (0.05% DEA) in CO2 from 5% to 40% Flow rate: 2.5 mL/min Wavelength: 220 nm.

Workup

  1. customRacemic-4,6-difluoro-5-[4-(tetrahydrofuran-2-yl)phenyl]-1H-indole-3-carboxylic acid was subjected to separation by preparative SFC (Column: OJ (250 MM*30 MM, 5 UM); Mobile phase: 30% MEOH NH3H2O 60 ML/MIN 3; Wavelength: 220 nm) Peak 1
  2. customwas isolated
  3. customPeak 1 was isolated as Isomer 1 (Example 152) Retention time=8.43 min
  4. customPeak 2 was isolated as Isomer 2 (Example 153), Retention time=8.86 min

Sources & evidence

ORD record
ord-7083ccffde82454d949f129dc160a5fe
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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